A new report on antimicrobial resistance from the European Centre for Disease Prevention and Control (ECDC) shows rising resistance to broad-spectrum antibiotics and multiple classes of antibiotics across Europe.

The annual report, based on data from 30 countries that report to the European Antimicrobial Resistance Surveillance Network (EARS-Net), is highlighted by an upward trend in resistance seen in gram-negative bacteria, particularly Escherichia coli and Klebsiella pneumoniae. The trends are seen in both individual member states and at the European Union/European Economic Area (EU/EEA) level.

K pneumoniae is a common cause of urinary tract, respiratory tract, and bloodstream infections in healthcare settings. E coli is the most frequent cause of urinary tract and bloodstream infections in Europe, and is commonly found both in healthcare and community settings.

The authors of the report call the findings on gram-negative bacteria "an especially worrying situation." A 2009 ECDC analysis estimated that drug-resistant bacteria were responsible for 25,000 deaths in Europe annually. With resistance levels rising, the authors write, that number is now likely to be considerably higher.

Rising resistance in E coli, K pneumoniae

Increasing resistance to third-generation cephalosporins was observed both in invasive E coli and K pneumoniae isolates, with the EU/EEA population-weighted mean percentage of third-generation cephalosporin-resistant E coli isolates rising from 11.9% in 2012 to 13.1% in 2015. In K pneumoniae isolates, continent-wide resistance to third-generation cephalosporins climbed from 25.8% in 2012 to 30.3% in 2015.

The report also notes that a large proportion of the isolates resistant to third-generation cephalosporins produced extended-spectrum beta-lactamase (ESBL) enzymes, which enable bacteria to resist many highly effective antibiotic classes. Infection with ESBL-producing gram-negative pathogens like E coli and K pneumoniae is associated with longer hospital stays and greater mortality.

In addition, an increase in combined resistance to fluoroquinolones, third-generation cephalosporins, and aminoglycosides was observed in both E coli and K pneumonia. At the EU/EEA level, combined resistance to the three drugs in E coli isolates rose from 4.9% in 2012 to 5.3% in 2015; in K pneumonia isolates, combined resistance rose from 17.7% to 18.6%.

According to the report, more than half of the E coli isolates reported to EARS-Net in 2015 were resistant to at least one class of the antimicrobials tested, while more than a third of the K pneumoniae isolates showed resistance to at least one antimicrobial drug.

"The observed increase in combined resistance to multiple antimicrobial groups, as well as the high proportion of ESBL-producing isolates, is especially worrying, as this leaves few treatment alternatives for patients suffering from infections caused by these pathogens," the authors write.

Among those treatment alternatives are carbapenems, which have the broadest spectrum of activity and are reserved for serious infections caused by drug-resistant pathogens. One of the concerns is that rising resistance to other drugs in gram-negative bacteria will lead to greater reliance on carbapenems, which will in turn contribute to the spread of carbapenem resistance.

Although most countries reported carbapenem resistance levels below 1%, the EU/EEA population-weighted mean for carbapenem resistance in K pneumoniae rose from 6.2% in 2012 to 8.1% in 2015. The report says the increase in carbapenem resistance in K pneumoniae is likely the result of an increase in isolates producing carbapenemase, an enzyme that neutralizes the drug. A November 2015 ECDC report called this increase "a cause for serious concern and a threat to patient safety in Europe."

The EARS-Net data also show significant levels of carbapenem resistance and multidrug resistance in Pseudomonas aeruginosa and Acinetobacter spp. Of the P aeruginosa isolates tested in 2015, 5.0% were resistant to carbapenems and 13.7% were resistant to at least three antimicrobial groups. Nearly 50% of Acinetobacter isolates showed combined resistance to fluoroquinolones, aminoglycosides, and carbapenems.

Carbapenem resistance levels remained low in E coli isolates across the 30 EU/EEA nations, at 0.1%.

Resistance varies by region

The annual report also shows that antimicrobial resistance levels in Europe continue to vary by geographic region, with countries in northern and western Europe generally having much lower levels of resistance than those in southern and eastern Europe. In Sweden, for example, only 1.1% of K pneumoniae invasive isolates tested in 2015 showed resistance to third-generation cephalosporins, compared with 69.5% in Greece.

"These differences are most likely related to difference in antimicrobial use, infection prevention, infection control practices, and healthcare utilisation patterns in the countries," the authors write.

One positive trend noted by the report was in Staphylococcus aureus. The EU/EEA population-weighted mean percentage of methicillin-resistant S aureus (MRSA) dropped 2 percentage points, falling from 18.8% to 16.8% in 2015.